Am. J. Respir. Crit. Care Med., Volume 161, Number 4, April 2000, 1179-1184

The Relationship between Chronic Hypoxemia and Activation of the Tumor Necrosis Factor- System in Patients with Chronic Obstructive Pulmonary Disease

NORIAKI TAKABATAKE, HIDENORI NAKAMURA, SHUICHI ABE, SUMITO INOUE, TOSHIHIKO HINO, HIROSHI SAITO, HIDEKI YUKI, SHUICHI KATO, and HITONOBU TOMOIKE

First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan

Although circulating tumor necrosis factor (TNF)- levels have been found to be increased in weight-losing patients with chronic obstructive pulmonary disease (COPD), the main causes for this phenomenon remain to be elucidated. Since hypoxia itself can enhance the production of the TNF- in vitro, we studied the relationship between hypoxemia and activities of the TNF- system, including circulating TNF- and soluble TNF-receptors (sTNF-R; sTNF-R55 and -R75) levels, in 27 COPD patients and 15 age-matched healthy controls. The COPD patients showed a significant weight loss (body mass index = 18.1 ± 2.8 versus 22.8 ± 2.2 [mean ± SD] kg/m²; p < 0.0001. % fat = 16.3 ± 5.9 versus 24.3 ± 4.9 %; p < 0.001), and hypoxemia (Pa_O2 = 62.2 ± 9.5 versus 88.6 ± 5.9 mm Hg; p < 0.0001) as compared with the healthy controls. Serum TNF- (6.15 ± 1.08 versus 5.41 ± 1.60 pg/ml; p < 0.05) and plasma sTNF-R55 (1.15 ± 0.49 versus 0.67 ± 0.13 ng/ml; p < 0.0001) and sTNF-R75 (3.54 ± 1.16 versus 2.25 ± 0.43; p < 0.0001) levels were significantly higher in the COPD patients than in the healthy controls. There were inverse correlations between Pa_O2 and circulating TNF- and sTNF-R levels in patients with COPD (TNF-; r = 0.426, p = 0.0297; sTNF-R55: r = 0.587, p = 0.0027; sTNF-R75: r = 0.573, p = 0.0035). In addition, we found inverse correlations between sTNF-R levels and % fat in COPD patients (sTNF-R55: r = 0.442, p = 0.0272; sTNF-R75: r = 0.484, p = 0.0155). TNF- levels correlated well with sTNF-R levels (sTNF-R55: r = 0.488, p = 0.0127; sTNF-R75: r = 0.609, p = 0.0019). These relationships were not observed in the healthy controls. These data suggest that systemic hypoxemia noted in patients with COPD is associated with activation of the TNF- system in vivo, which may be a factor contributing to the weight loss in patients with the disease.

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